The evaluation of hepatic histology and treatment of hepatitis C virus (HCV)/HIV-coinfected patients is rapidly changing. HCV has become an important cause of mortality in HIV-infected patients. Consequently, assessment of liver histology in all coinfected patients is particularly important. The evaluation of hepatic histology is shifting from reliance on the liver biopsy toward noninvasive modalities. Additionally, the importance of HCV-associated morbidity and mortality in HIV-infected patients has prompted increasing numbers of these patients to be HCV treatment candidates. Prospective trials in coinfected patients have reported lower sustained virologic responses compared to HCV-monoinfected patients. Consequently, the numbers of coinfected nonresponders to pegylated interferon/ribavirin continues to increase. Because none of the presently available treatment modalities for pegylated interferon/ribavirin nonresponders are clearly efficacious, management decisions must be individualized. The options include, HCV-specific medications, maintenance therapy, the use of alternative interferon formulations, and observation. HCV-specific agents, particularly protease and polymerase inhibitors, show early promise in HCV-monoinfected individuals. Their use in coinfected patients, however, is likely to be delayed for several years, and they are likely to be used in combination with interferon. Low-dose pegylated interferon, administered in an attempt to slow fibrosis progression (maintenance therapy), is being evaluated in several large prospective trials in monoinfected and coinfected patients. Observation may be best for nonresponders with relatively mild hepatic histology. In summary, HCV treatment will likely follow the example forged by HIV. In the near future, combinations of different drugs will likely be used simultaneously to result in durable viral suppression.